1. New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 M pro inhibitory activities.
- Author
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Li Q, Yang PY, Peng C, Zhang XJ, Jiang YT, Li YP, and Gao L
- Subjects
- Humans, Molecular Structure, Antiviral Agents pharmacology, Antiviral Agents chemistry, Antiviral Agents isolation & purification, Animals, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents isolation & purification, Dose-Response Relationship, Drug, Structure-Activity Relationship, COVID-19 Drug Treatment, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal isolation & purification, Polyketides chemistry, Polyketides pharmacology, Polyketides isolation & purification, Ascomycota chemistry, Terpenes chemistry, Terpenes pharmacology, Terpenes isolation & purification, SARS-CoV-2 drug effects, Coronavirus 3C Proteases antagonists & inhibitors, Coronavirus 3C Proteases metabolism, Coronavirus 3C Proteases chemistry
- Abstract
Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of
1 H,13 C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC50 values of 1.78 μM and 1.54 μM, respectively. Moreover, they inhibited the secretion of IL-1β and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 Mpro ), with IC50 values of 10.8 ± 0.9 μM and 12.9 ± 0.7 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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